The present study introduces a miniaturized high-throughput platform to understand the influence of excipients on the performance of oral solid dosage forms during early drug development. Wet massing of binary mixtures of the model drug (sodium naproxen) and representative excipients was followed by sieving, drying, and compaction of the agglomerated material. The mini-compacts were subjected to stability studies at 25°C/5% relative humidity (RH), 25°C/60% RH and 40°C/75% RH for 3 months. The physical stability of the drug was affected by the storage condition and by the characteristics of the excipients, whereas all the samples were chemically stable. Force-distance curves obtained during the compression of agglomerated material were used for the comparison of compressibility of different drug-excipient mixtures. The agglomerated drug-excipient mixtures were also subjected to studies of the dissolution trend under sequential pH conditions to simulate pH environment of gastrointestinal tract. Major factors affecting the dissolution behavior were the diffusion layer pH of the binary mixtures and the ability of the excipients to alter the diffusion layer thickness. The proposed approach can be used for excipient selection and for early-stage performance testing of active pharmaceutical ingredient intended for oral solid dosage form.
Keywords: co-crystal; compression; dissolution; excipients; hydrate; pH; phase transition; preformulation; salts; stability.
© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.